Use of homologous platelet gel to manage refractory diabetic lower extremity ulcers: additional experience at a tertiary hospital.

BACKGROUND: DLEUs are a major cause of morbidity. Appropriate treatment is essential, and newer methods to achieve ulcer healing have been described, including application of PG. OBJECTIVE: This study evaluated the effectiveness and safety of homologous PG in patients with chronic noninfected DLEU refractory to standard treatment as well as possible correlations between patient comorbidities and response to treatment. MATERIALS AND METHODS: Data from patients with chronic refractory DLEU managed with homologous PG between January 2014 and October 2022 were evaluated (comorbidities, wound characteristics, number and time of treatment, outcome). Outcome was classified as complete response (complete ulcer healing with reepithelialization), partial response (≥50% reduction in area and/or improvement of pain), or absence of response. The chi-square test was used to compare groups, with alpha level set at less than .05. RESULTS: A total of 81 patients (63 male, 18 female; median age, 65 years; median HbA1c, 7.6%; median ulcer area, 2.9 cm2) were proposed for PG application. A total of 62 patients had 3 or more comorbidities. Outcome was evaluated in 69 patients, with response observed in 49% (complete, 32%; partial, 17%). Worse outcomes occurred in patients with polyneuropathy (chi-square statistic: 4.183; P = .041). CONCLUSION: Homologous PG is a safe and possibly effective therapeutic alternative for DLEU that is unresponsive to standard therapies.

Fabry Disease p.M290I Mutation is Related to Organ Involvement: A Case Report.

Fabry disease (FD) is an X-linked hereditary disease. It results from mutations in the GLA gene, leading to deficient activity of the enzyme alpha-galactosidase A (α-Gal A) and progressive accumulation of undegraded glycosphingolipids in cell lysosomes. Enzyme replacement therapy (ERT) can improve the natural course of this disease, but an early diagnosis is crucial for a successful treatment. We describe the case of a female diagnosed with chronic proteinuric kidney disease in the postpartum period. Despite receiving optimal medical treatment, the disease progressed and she started renal replacement therapy (RRT) with peritoneal dialysis (PD). Five years later, she was enrolled in a pilot screening study for FD, and the heterozygous mutation c.870G>C (p.Met290Ile; M290I) in exon six of the GLA gene was found. The family screening revealed the presence of this mutation in the patient's father and daughter. The proband did not meet the criteria for a definitive FD diagnosis, but she remained under follow-up at our nephrology metabolic diseases consultation, as the mutation was described as pathogenic and associated with a classic FD phenotype. Later that same year, reassessment exams revealed a worsening left ventricle mass index (LVMi), a new ischemic cerebral lesion, and a substantial increase in serum globotriaosylsphingosine (LysoGb3) levels. These clinical changes led to a decision to initiate ERT. p.M290I is a previously known but poorly described GLA mutation. To our knowledge, this is the first report of p.M290I mutation-associated disease activity that offers strong evidence of its pathogenicity.

Evolutionary trends in bacteria isolated from moderate and severe diabetic foot infections in a Portuguese tertiary center.

INTRODUCTION: Diabetic Foot infections (DFI) are a major cause of hospitalization in patients with diabetes. The microbiological study of diabetic ulcers is essential to adequate antibiotic therapy and to minimize the selection of resistant microorganisms. The aim of this study was to characterize and to compare the evolution of isolated microorganisms between the biennium 2010-2011 and 2016-2017, in hospitalized patients with DFI. MATERIAL AND METHODS: Retrospective evaluation of the clinical and analytical data of patients who were admitted due to DFI in 2010-2011 (group 2010/11) and 2016-2017 (group 2016/17). Only the first hospitalization for each patient was included. An adequate descriptive and comparative statistical analysis was performed. RESULTS: There were 274 admissions due to DFI, 151 in 2010/11 and 123 in 2016/17. There was an increase in admissions due to neuroischemic DFI (51.0% in 2010/11 to 61.8% in 2016/17, p = 0.048). Staphylococcus aureus (SA) was the most common isolate in 2010/11 (26.7%). In 2016/17 most cultures were mixed polymicrobial and isolation of Enterobacteriaceae and Pseudomonas aeruginosa increased from 2010/11 to 2016/17 (15.9% to 30.6%, p = 0.001, and 9.1% to 13.7%, p = 0.048, respectively). CONCLUSION: There was an increase in the prevalence of neuroischemic DFU. The Enterobacteriaceae family replaced SA as the most prevalent pathogen in DFI, with an increase in the isolation of gram-negative microorganisms and mixed polymicrobial cultures. Chronic neuroischemic infected ulcers usually present distinct bacterial isolates; knowledge about the most common agents is warranted in order to better select empiric antibiotic therapy.

Topic platelet gel application in chronic diabetic foot ulcers.

In this observational study performed during 45 months we evaluated patients with chronic and recalcitrant diabetic ulcers who were treated with homologous platelet gel. METHODS: platelet gels were obtained from homologous platelet concentrates that were aliquoted and freezed, being then activated with calcium gluconate and applied in the ulcer after cleaning and debridement. We evaluated patient's comorbidities, wound characteristics (size, tissue, inflammatory signs, pain), number and time of treatment as well as outcome (classified as complete epithelialization; partial improvement- 50% reduction in wound size or pain relief; no evolution). RESULTS: Fifty-two patients (42 males, 10 females), with a median age of 65 years (range 43-85) were proposed for platelet gel. The following associated comorbidities were observed: hypertension (n = 41), dyslipidemia (n = 29), polyneuropathy (n = 30), peripheral arteriopathy (n = 32), retinopathy (n = 21), nephropathy (n = 15), cardiac ischemic disease (n = 14), obesity (n = 9). Thirty-eight patients presented with 3 or more associated comorbidities. The more frequent ulcer locations were sole of the foot (n = 13) and heel (n = 10). The median number of applications was 16, during 8.5 weeks. Nineteen patients (44%) achieved complete healing, 3 patients (7%) had a partial response and 21 (49%) had no progression. We did not observe a statistically significant relationship between patient age and response nor between number of comorbidities and response. We observed a more favorable evolution in patients with good compliance and good glycemic control. CONCLUSION: Platelet gel is an effective therapeutic alternative, provided compliance and effective metabolic control are ensured.

The experimental model of nephrotic syndrome induced by Doxorubicin in rodents: an update.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. It begins by changes in the glomerular filtration barrier, with increased permeability to plasma proteins. It affects all age groups and can progress to end-stage renal disease. NS pathophysiology is still unknown. However, the critical role of the immune system is well recognized. Animal models are useful tools for the investigation of NS. Among different experimental models proposed in the literature, disease induced by Doxorubicin has been considered helpful to the purpose of many studies. The aim of this review article is to describe the animal model of NS induced by the injection of Doxorubicin in rodents, with emphasis on action of the drug, potential mechanisms of renal injury, as well biochemical, histological, and corporal changes obtained with this model.

Is dental caries experience increased in HIV-infected children and adolescents? A meta-analysis.

OBJECTIVE: To undertake a systematic review to assess if HIV-infected children and adolescents have an increased dental caries experience. METHODS: A search of MEDLINE, BIREME, EMBASE, GOOGLE SCHOLAR, SIGLE (Grey Literature) and reference lists of included studies was carried out. To be eligible the studies had to present HIV-infected and non-infected children/adolescents between 0-18 years old. To assess the methodological quality, the studies were categorized in scores from 'A' to 'C'. To perform a meta-analysis a random effect model was used with 95% confidence intervals and two distinct sub-group analyses were carried out in terms of caries progression: data for cavitated and non-cavitated lesions (sub-group 1) and data only for cavitated lesions (sub-group 2). RESULTS: Five studies fulfilled the selection criteria. Four studies (two ranked A and two B in the quality assessment) revealed higher caries scores in primary teeth in the HIV-infected patients with mean dmft/dmfs scores of 3.8-4.1/7.8-11.0 compared to the control group 1.5-2.4/3.4-5.1. No differences in caries index were found for permanent dentition. The meta-analysis excluded caries data of permanent teeth and showed a significant association between caries experience in primary dentition and HIV infection considering cavitated and non-cavitated lesions (OR = 2.33, 95% CI = 1.48-3.68) or only cavitated lesions (OR = 2.98, 95% CI = 1.59-5.59). CONCLUSION: Evidence exists that suggests HIV-infected children/adolescents have an increased caries experience in primary dentition.

PAX2 polymorphisms and congenital abnormalities of the kidney and urinary tract in a Brazilian pediatric population: evidence for a role in vesicoureteral reflux.

BACKGROUND AND OBJECTIVES: Congenital anomalies of the kidney and urinary tract (CAKUT) are common genetic malformations. Since the PAX2 gene has a role in kidney organogenesis, this study investigated the association of PAX2 gene polymorphisms with CAKUT in general and with specific phenotypes of CAKUT in a Brazilian pediatric population. METHODS: This study included 241 individuals with antenatal hydronephrosis and 259 healthy controls. For genotyping and allelic discrimination we used the probes to rs2077642, rs4244341, rs6421335, rs11190698, and rs11190693. RESULTS: No statistical differences in allele and genotype frequencies were observed for the single nucleotide polymorphism (SNP) rs11190693. At the SNPs rs4244341 and rs11190698, the frequencies of the ancestral alleles were significantly higher among CAKUT patients (rs4244341 allele G: 0.86 vs. 0.78; rs11190698 allele A: 0.85 vs. 0.79). At the SNP rs4244341, the genotype GG was increased in CAKUT group (0.72 vs. 0.61, P = 0.013), while the TT was higher in controls (0.01 vs. 0.05, P = 0.001). At the SNP rs11190698, the genotype CC was increased in controls (0.02 vs. 0.06, P = 0.01). The most frequent CAKUT phenotypes were vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK), and ureteropelvic junction obstruction (UPJO). In patients with VUR, the frequencies of the monozygotic ancestral alleles decreased at the SNP rs11190693 (AA 0.13 vs. 0.26, P = 0.04) and increased at the SNP rs4244341 (GG 0.77 vs. 0.61, P = 0.03). No statistical differences were detected between controls and patients with UPJO and with MCDK for all SNPs. CONCLUSION: The PAX2 gene seems to be involved with the pathogenesis of VUR in our sample.

The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies.

Idiopathic nephrotic syndrome (INS) is a multifactorial disease, characterized by proteinuria, hypoalbuminemia, edema and hyperlipidemia. Studies in humans and animal models have associated INS with changes in the immune response. The purpose of this article is to review clinical and experimental findings showing the involvement of the immune response in the pathogenesis of INS. The role of the immune system in INS has been shown by clinical and experimental studies. However, the pattern of immune response in patients with INS is still not clearly defined. Many studies show changes in the dynamics of T lymphocytes, especially the regulatory T cells. Alternatively, there are other reports regarding the involvement of the complement system and B lymphocytes in the pathophysiology of INS. Indeed, none of the immunological biomarkers evaluated were undeniably linked to changes in glomerular permeability and proteinuria. On the other hand, some studies suggest a link between urinary chemokines, such as IL-8/CXCL8 and MCP-1/CCL2, and changes in glomerular permeability and/or the deterioration of glomerulopathies. To understand the pathophysiology of INS, longitudinal studies are clearly needed. The characterization of the profile of the immune response might help the development of specific and individualized therapies, leading to clinical improvement and better prognosis.

[The Neuropad test in the screening of peripheral neuropathy in diabetic patients]. / O teste com Neuropad na detecção precoce da neuropatia periférica do doente diabético.

One of the first signs of peripheral neuropathy is the loss of perspiration of the feet. Untill now, the Semmes-Weinstein monofilament test has been considered the gold test to detect early peripheral neuropathy. Recently, the Neuropad test has become available: it is a cobalt salt plaster designed to change colour from blue to pink in contact with liquids, namely sweating. The objective of this study was to find if the Neuropad test could be considered as a test for detecting peripheral autonomic neuropathy and to compare its sensitivity and specificity to the Semmes-Weinstein monofilament test. Forty diabetic patients were studied, 22 of them presented with peripheral neuropathy. The criteria used for the definition of neuropathy was based on the Neuropathy Disability Score (NDS). Under Semmes-Weinstein monofilament test, we found a sensitivity and specificity of 82% and 94%, respectively, and with the Neuropad test, a specificity of 44%, but a sensitivity of 100%. Ten patients presented a sudomotor dysfunction of the feet in the absence of peripheral neuropathy (based on the NDS criteria), and were considered as false positives. We concluded that the Neuropad test is a simple, sensitive test to screen for diabetic neuropathy. Based on the false positive results, we may consider it as a reliable test detecting neuropathy in a earlier phase.